Validation of the IWATE Criteria in Robotic-Assisted Liver Resections.

Background/Objectives: The IWATE criteria are well-established as a helpful tool to preoperatively estimate the difficulty and perioperative outcome of laparoscopic liver resections. We evaluated the relationship between the IWATE criteria and the perioperative outcomes in robotic-assisted liver resections (RARLs). Methods: We retrospectively analyzed the data of 58 patients who underwent robotic-assisted liver surgery at our center between July 2019 and April 2023. The operative difficulty of every patient was graded according to the IWATE criteria and compared to the perioperative outcome. Results: The median operation time was 236.5 min (range 37-671 min), and the median length of stay was 6 days (range 3-37 min). The majority had no complications (65.5%; n = 38), 18 (31.0%) patients suffered from mild complications (CD ≤ 3A) and 2 patients (3.4%) suffered from relevant complications (CD ≥ 3B). We observed no deaths within 30 postoperative days. The surgery time, postoperative ICU stay and perioperative blood transfusions increased significantly with a higher difficulty level (p = < 0.001; p < 0.001; p = 0.016). The length of stay, conversion to open surgery (n = 2) and complication rate were not significantly linked to the resulting IWATE group. Conclusions: The IWATE criteria can be implemented in robotic-assisted liver surgery and can be helpful in preoperatively estimating the difficulty of robotic liver resections. Whether there is a "robotic effect" in minimally invasive liver resections has to be further clarified. The IWATE criteria can help to develop curricula for robotic training.

Extracellular vesicles as potential biomarkers for diagnosis and recurrence detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. However, current diagnostic tools are often invasive and technically limited. In the last decade, non-invasive liquid biopsies have transformed the field of clinical oncology, showcasing the potential of various liquid-biopsy derived analytes, including extracellular vesicles (EVs), to diagnose and monitor HCC progression and metastatic spreading, serving as promising novel biomarkers. A prospective single-center cohort study including 37 HCC patients and 20 patients with non-malignant liver disease (NMLD), as a control group, was conducted. Serum EVs of both groups were analyzed before and after liver surgery. The study utilized microbead-based magnetic particle sorting and flow cytometry to detect 37 characteristic surface proteins of EVs. Furthermore, HCC patients who experienced tumor recurrence (R-HCC) within 12 months after surgery were compared to HCC patients without recurrence (NR-HCC). EVs of R-HCC patients (n = 12/20) showed significantly lower levels of CD31 compared to EVs of NR-HCC patients (p = 0.0033). EVs of NMLD-group showed significantly higher expressions of CD41b than EVs of HCC group (p = 0.0286). The study determined significant short-term changes in CD19 dynamics in EVs of the NMLD-group, with preoperative values being significantly higher than postoperative values (p = 0.0065). This finding of our pilot study suggests EVs could play a role as potential targets for the development of diagnostic and therapeutic approaches for the early and non-invasive detection of HCC recurrence. Further, more in-depth analysis of the specific EV markers are needed to corroborate their potential role as diagnostic and therapeutic targets for HCC.

Left septal fascicular block: Evidence, causes, and diagnostic criteria.

The existence of a tetrafascicular intraventricular conduction system is widely accepted by researchers. In this review, we have updated the criteria for left septal fascicular block (LSFB) and the differential diagnosis of prominent anterior QRS forces. More and more evidence points to the fact that the main cause of LSFB is critical proximal stenosis of the left anterior descending coronary artery before its first septal perforator branch. The most important characteristic of LSFB that has been incorporated in the corresponding diagnostic electrocardiographic criteria is its transient/intermittent nature mostly observed in clinical scenarios of acute (ie, acute coronary syndrome including vasospastic angina) or chronic (ie, exercise-induced ischemia) ischemic coronary artery disease. In addition, the phenomenon proved to be phase 4 bradycardia rate dependent and induced by early atrial extrastimulus. Finally, we believe that intermittent LSFB has the same clinical significance as "Wellens syndrome" and the "de Winter pattern" in the acute coronary syndrome scenario.

Postoperative infectious complications are associated with diminished overall survival of patients undergoing resection for colorectal liver metastases.

INTRODUCTION: Postoperative infectious complications (PIC) remain one of the most common complications after surgery. The influence of PIC on long-term survival for patients after liver surgery for colorectal liver metastases (CRLM) needs further investigation. METHODS: Data of patients who underwent liver resection for CRLM between 2012 and 2017 at the Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin were evaluated. Overall survival (OS) was stratified according to the development of PIC. Independent predictors of PIC and diminished survival were identified using regression models. RESULTS: Of 270 patients, eighty-four (31%) patients developed PIC including intraabdominal infections (n = 51, 61%), cholangitis (n = 5, 6%), pneumonia (n = 12, 14%), wound infections (n = 28, 33%), urinary tract infections (n = 5, 6%), or central line-associated bloodstream infections (n = 4, 5%). PIC were associated with a significantly diminished five-year OS (30% vs. 43%, p = 0.008). Age >65 years (p = 0.016, hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.2-4.0), comorbidity (p = 0.019, HR [95% CI] = 2.4 [1.2-4.9]), simultaneous resection of primary tumor (p = 0.005, HR [95% CI] = 4.3 [1.6-11.9]), biliary drainage (p < 0.001, HR [95% CI] = 4.1 [2.0-8.5]), and length of procedure ≥272 min (p = 0.012, HR [95% CI] = 2.2 [1.2-4.1]) were independent predictors for the development of PIC. Body-mass index (BMI) > 30 kg/m2 (p = 0.002, HR [95% CI] = 2.4 [1.4-4.0]), postoperative major complications (p = 0.003, HR [95% CI] = 2.2 [1.3-3.8]), and 3- or 4-MRGN bacteria (p = 0.001, HR [95% CI] = 7.7 [2.2-27.3]) were independently associated with diminished OS. CONCLUSIONS: PIC are associated with diminished OS after resection for CRLM. Age >65 years, comorbidities, simultaneous resection of the primary tumor, and biliary drainages were identified as independent risk factors for the development of PIC. High BMI, postoperative major morbidity and 3-/4-MRGN bacteria were independently predictive of worse OS. These factors need to be considered in perioperative management for patients with CRLM.

Resection margin status at the portomesenteric axis may not determine oncologic outcome after pancreaticoduodenectomy for lymph node-positive pancreatic ductal adenocarcinoma.

BACKGROUND: Lymph node and resection margin status are associated with oncologic outcomes after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. However, surgical radicality at the portomesenteric axis in case of suspected infiltration remains controversial. METHODS: Clinicopathological data of patients who underwent a partial or total pancreaticoduodenectomy for PDAC between 2012 to 2019 in 2 major hepato-pancreato-biliary centers in Germany and Switzerland were assessed. We evaluated the impact of positive resection margins at the vascular, parenchymal, and retropancreatic surfaces on overall survival in patients with and without lymph node involvement. Margin-positive vascular resection included both patients with positive margins at the vascular groove and the resected venous wall. RESULTS: During the study period, 217 patients underwent partial/total pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. After excluding 7 patients suffering postoperative complications resulting in mortality within 90 days after surgery (3%), 169 patients had lymph node involvement (80%). In the entire study cohort, margin-positive resection (33%) was significantly associated with worse overall survival (3-year overall survival: margin-positive resection: 27% vs margin-negative resection: 43%, P = .014). Among patients with positive lymph nodes, margin-positive vascular resection (n = 48, 28%) was not significantly associated with impaired overall survival (3-year overall survival: margin-positive vascular resection: 28% vs margin-negative vascular resection: 36%, P = .065). On the contrary, margin-positive parenchymal resection (n = 7, 4%) (3-year overall survival: margin-positive parenchymal resection: 0% vs margin-negative parenchymal resection: 35%, P < .0001) and margin-positive retropancreatic resection (n = 21, 12%) (3-year overall survival: margin-positive retropancreatic resection: 6% vs margin-negative retropancreatic resection: 39%, P < .0001) significantly diminished overall survival in univariate and multivariate analysis in all patients. Among patients without lymph node involvement (n = 41, 20%), there were no margin-positive parenchymal or margin-positive retropancreatic resections. In contrast, only 5 patients had margin-positive vascular resection (12%), with overall survival compared to those with margin-negative vascular resection. CONCLUSIONS: In patients with pancreatic ductal adenocarcinoma and lymph nodal positivity, resection status at the parenchymal and retropancreatic surface but probably not at the portal and/or superior mesenteric vein is a determinant of survival. Therefore, margin-negative resection should be pursued during pancreaticoduodenectomy. However, radical venous resection and/or reconstruction for suspected tumor infiltration may not be necessary for patients with intraoperatively detected lymph node metastases.

Inhibition of Vascular Endothelial Growth Factor Protects against the Development of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome in Wild-Type but Not in CD39-Null Mice.

(1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model. (2) Methods: Male wild-type and CD39-null mice received oxaliplatin, additional anti-VEGF (OxAV), or controls, and were sacrificed or subjected to major partial hepatectomy (MH). Specimen were used for histological analysis of SOS. Liver damage was assessed by plasma transaminases. The VEGF pathway was elucidated by quantitative PCR of liver tissue and protein analysis of plasma. (3) Results: Mice treated with oxaliplatin developed SOS. Concomitant anti-VEGF facilitated a reduced incidence of SOS, but not in CD39-null mice. SOS was associated with increased plasma VEGF-A and decreased hepatocyte growth factor (HGF). After OxAV treatment, VEGF-R2 was upregulated in wild-type but downregulated in CD39-null mice. Oxaliplatin alone was associated with higher liver damage after MH than in mice with concomitant VEGF-inhibition. (4) Conclusions: We established a murine model of oxaliplatin-induced SOS and provided novel evidence on the protective effect of VEGF-inhibition against the development of SOS that may be associated with changes in the pathway of VEGF and its receptor VEGF-R2.

Standardization of Synthetic Biology Tools and Assembly Methods for Saccharomyces cerevisiae and Emerging Yeast Species.

As redesigning organisms using engineering principles is one of the purposes of synthetic biology (SynBio), the standardization of experimental methods and DNA parts is becoming increasingly a necessity. The synthetic biology community focusing on the engineering of Saccharomyces cerevisiae has been in the foreground in this area, conceiving several well-characterized SynBio toolkits widely adopted by the community. In this review, the molecular methods and toolkits developed for S. cerevisiae are discussed in terms of their contributions to the required standardization efforts. In addition, the toolkits designed for emerging nonconventional yeast species including Yarrowia lipolytica, Komagataella phaffii, and Kluyveromyces marxianus are also reviewed. Without a doubt, the characterized DNA parts combined with the standardized assembly strategies highlighted in these toolkits have greatly contributed to the rapid development of many metabolic engineering and diagnostics applications among others. Despite the growing capacity in deploying synthetic biology for common yeast genome engineering works, the yeast community has a long journey to go to exploit it in more sophisticated and delicate applications like bioautomation.

Liver Resection for Primary Hepatic Angiosarcoma: Bicentric Analysis of a Challenging Entity.

Primary hepatic angiosarcoma (PHA) is a rare malignant tumor of the liver, and data on patient outcome after surgical treatment are scarce. The aim of this study was to evaluate postoperative morbidity and overall survival (OS) of patients who underwent hepatectomy for PHA. This is a bicentric retrospective analysis of all consecutive patients who underwent liver resection in curative intent for PHA between 2012 and 2019 at the University Hospital of Muenster and the University Hospital of Bern. Nine patients (five female, four male) were included from both centers. Median age was 72 years (44-82). Most lesions (77.8%) were larger than 5 cm, and mean size of the biggest lesion was 9.4 ± 4.5 cm. Major hepatectomy was performed in four (44.4%), and radical resection (R0) was achieved in six (66.7%) patients. Postoperative complication rate was 88.8%, including 44.4% higher than 3a in the Clavien-Dindo classification. OS survival rates at 1, 2, and 3 years were 44.4%, 22.2%, and 12.5%, respectively, and median OS was 5 months. OS was significantly better after radical resection (R0: 15 months vs. R1: 0 months, p = 0.04), whereas presentation with tumor rupture at diagnosis was associated with the worst OS (0 months vs. 15 months, p = 0.005). Disease recurrence occurred in three patients (33.3%) between three and seven months after surgery. Radical resection remains the only potentially curative treatment option for PHA. However, postoperative morbidity is high, and the overall prognosis remains poor. Multimodal therapy options and management strategies are urgently needed and could improve the prognosis of patients suffering from PHA in the future.

High tumor mutational burden (TMB) identifies a microsatellite stable pancreatic cancer subset with prolonged survival and strong anti-tumor immunity.

AIM: Tumor mutational burden (TMB: somatic mutations per megabase, mut/Mb) predicts the efficacy of immunotherapy. Here, we link TMB levels with the activation of immune pathways and intratumoral immune responses in pancreatic adenocarcinoma (PDAC) to explore immunoarchitectural patterns associated with high TMB. METHODS: We assessed TMB in 161 resected, microsatellite stable (MSS) PDACs, including 41 long-term survivors (LTS). Five microsatellite instable (MSI-high) cases were also assessed. Cases were classified into TMB-high (≥10 mut/Mb), TMB-intermediate (>5 < 10 mut/Mb), and TMB-low (≤5 mut/Mb) categories. Tumors additionally underwent mRNA in situ hybridization for immune pathway genes and were immunoprofiled by multiplex immunofluorescence followed by automated image analysis. RESULTS: We detected 12 TMB-high, 28 TMB-intermediate, and 121 TMB-low cases. TMB-high tumors comprised ten LTSs (10/41; 24%) and two conventional PDACs (2/120; 1.7%). They exhibited the highest T cell density with significantly increased CD3+CD4+T helper and CD208+dendritic cell (DC) counts, compared to all other cases. CD3+CD8+cytotoxic T cells were significantly closer to tumor cells and T helper cells closer to DCs in TMB-high PDACs. Immune pathways involved in T cell activation, immune cell adhesion/migration, antigen presentation, and cytokine signaling were upregulated in most TMB-high and many TMB-intermediate tumors. ARID1A and ERBB4 alterations were more frequent in TMB-high PDACs. All MSI-high PDACs were TMB-high. CONCLUSIONS: TMB-high cases frequently belong to specific PDAC subsets with prolonged survival such as LTSs and MSI-high PDACs. They display strong anti-tumor immune responses fueled by a T helper cell/DC-mediated priming of the cytotoxic T cells. Moreover, they frequently harbor further actionable alterations.

Understanding Online and Offline Social Networks in Illness Management of Older Patients With Asthma and Chronic Obstructive Pulmonary Disease: Mixed Methods Study Using Quantitative Social Network Assessment and Qualitative Analysis.

BACKGROUND: Individuals' social networks and social support are fundamental determinants of self-management and self-efficacy. In chronic respiratory conditions, social support can be promoted and optimized to facilitate the self-management of breathlessness. OBJECTIVE: This study aimed to identify how online and offline social networks play a role in the health management of older patients with chronic respiratory conditions, explore the role of support from online peers in patients' self-management, and understand the barriers to and potential benefits of digital social interventions. METHODS: We recruited participants from a hospital-run singing group to a workshop in London, the United Kingdom, and adapted PERSNET, a quantitative social network assessment tool. The second workshop was replaced by telephone interviews because of the COVID-19 lockdown. The transcripts were analyzed using thematic analysis. RESULTS: A total of 7 participants (2/7, 29%, men and 5/7, 71%, women), with an age range of 64 to 81 years, produced network maps that comprised between 5 and 10 individuals, including family members, health care professionals, colleagues, activity groups, offline and online friends, and peers. The visual maps facilitated reflections and enhanced participants' understanding of the role of offline and online social networks in the management of chronic respiratory conditions. It also highlighted the work undertaken by the networks themselves in the self-management support. Participants with small, close-knit networks received physical, health, and emotional support, whereas those with more diverse and large networks benefited from accessing alternative and complementary sources of information. Participants in the latter type of network tended to communicate more openly and comfortably about their illness, shared the impact of their illness on their day-to-day life, and demonstrated distinct traits in terms of identity and perception of chronic disease. Participants described the potential benefits of expanding their networks to include online peers as sources of novel information, motivation, and access to supportive environments. Lack of technological skills, fear of being scammed, or preference for keeping illness-related problems for themselves and immediate family were reported by some as barriers to engaging with online peer support. CONCLUSIONS: In this small-scale study, the social network assessment tool proved feasible and acceptable. These data show the value of using a social network tool as a research tool that can help assess and understand network structure and engagement in the self-management support and could be developed into an intervention to support self-management. Patients' preferences to share illness experiences with their online peers, as well as the contexts in which this can be acceptable, should be considered when developing and offering digital social interventions. Future studies can explore the evolution of the social networks of older people with chronic illnesses to understand whether their willingness to engage with online peers can change over time.

Transitory R wave growth in the midst of ST-segment elevation myocardial infarction: A case of left septal fascicular block with atypical electrocardiographic presentation.

We report the case of a patient who presented with angina and ST-segment elevation in the precordial leads owing to a proximal occlusion of the left anterior descending coronary artery. Serial electrocardiography (ECG) showed signs consistent with the left septal fascicular block (LSFB). The latter was observed in conjunction with a pre-existing left anterior fascicular block and presented atypical ECG features, such as intermittent prominent anterior QRS forces (prominent R wave) in V2 only and preserved septal q waves in I and aVL. In the discussion, we present an overview of the electrocardiographic criteria for the diagnosis of the LSFB together with reasons for which LSFB may present with an atypical ECG picture.